3-(5-(Tert-butyl)-2-((2-methoxyethoxy)methoxy)phenyl)-6-(trifluoromethyl)pyridazine → 4-(Tert-butyl)-2-(6-(trifluoromethyl)pyridazin-3-yl)phenol

HRID 1480630Notes

Reaction equation

HRID 1480630 reaction equation
[C:1]([C:5]1[CH:6]=[CH:7][C:8]([O:21]COCCOC)=[C:9]([C:11]2[N:12]=[N:13][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:15][CH:16]=2)[CH:10]=1)([CH3:4])([CH3:3])[CH3:2]>CO.Cl>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([OH:21])=[C:9]([C:11]2[N:12]=[N:13][C:14]([C:17]([F:19])([F:20])[F:18])=[CH:15][CH:16]=2)[CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 867185903-(5-(Tert-butyl)-2-((2-methoxyethoxy)methoxy)phenyl)-6-(trifluoromethyl)pyridazine

Product 1

HCID 1364080954-(Tert-butyl)-2-(6-(trifluoromethyl)pyridazin-3-yl)phenolYield 81%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Procedure

A solution of 3-(5-(tert-butyl)-2-((2-methoxyethoxy)methoxy)phenyl)-6-(trifluoromethyl)pyridazine (0.452 g, 1.18 mmol) in methanol (50 mL) and 1.0M aqueous hydrochloric acid (25 mL) was stirred at 60° C. for 5 hours. The cooled reaction mixture was then concentrated under reduced pressure to remove methanol. The resulting aqueous suspension was partitioned between ethyl acetate (80 mL) and saturated aqueous sodium hydrogen carbonate solution (80 mL), the organic phase separated, washed with water (80 mL) and saturated brine (80 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give a cream solid. The crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 20% ethyl acetate in hexanes to give 4-(tert-butyl)-2-(6-(trifluoromethyl)pyridazin-3-yl)phenol (0.282 g, 81% yield) as a cream solid.

Workup

  1. customThe cooled reaction mixture
  2. concentrationwas then concentrated under reduced pressure
  3. customto remove methanol
  4. customThe resulting aqueous suspension was partitioned between ethyl acetate (80 mL) and saturated aqueous sodium hydrogen carbonate solution (80 mL)
  5. customthe organic phase separated
  6. washwashed with water (80 mL) and saturated brine (80 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto give a cream solid
  11. customThe crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-000befaca042409f9fdfdcb69319c772
Source dataset
uspto-grants-2016_08
Patent number
US09409893B2

Reaction notes

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